CANCER BIOLOGY AND BIOCHEMISTRY PROGRAM Project Summary The Cancer Biology and Biochemistry Program (CBB) is a continuation of the former Cellular Damage and Defense Program that earned an ?outstanding? rating during the last CCSG renewal. During the most recent funding period, the overall scientific theme of the Program further coalesced around cancer biology and biochemistry, with three established themes clearly delineated: Redox Modulation, Genomic Integrity, and Cellular Metabolism. These themes have been strengthened through faculty development and recruitment, consistent with the evolution and growth of the Program. Importantly, the themes are designed to meet the scientific needs of the catchment area. As noted in the Director's Overview and the Cancer Prevention and Control Program, smoking is highly prevalent in the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) catchment population. Tobacco smoke is well-known to induce reactive oxygen species and DNA damage in cells. Moreover, reactive oxygen species induce DNA damage, and both reactive oxygen species and DNA damage result in aberrant cellular metabolism. These processes are intimately involved in other cancer-related processes driven by oncogenes, therapeutic response, radiation response, and inflammation, to name a few. The cancer research landscape reflects the interconnection among the pathways involved in these processes. As a result, there has been targeted recruitment of investigators who engage in these three themes and bring expertise that promotes expansion and evolution of the science. The Program and WFBCCC leadership, in concert with WFBCCC External Advisory Board, decided that a name change was appropriate to more easily define and encompass the scientific activities of the Program investigators. Importantly, the name accurately reflects the overall scientific expertise of the Program members, the major departmental affiliations within the institution, and the continued thematic development by the Program leadership. The goals of the Program are to understand how biochemistry shapes cancer cell origin and to translate these findings towards human interventions, in collaboration with the Clinical Research Program. The goals of the Program are achieved through the following Specific Aims to: 1) Determine how specific biochemical pathways affect tumor initiation and development; and 2) Develop novel therapeutic strategies to improve cancer therapy. The CBB Program is composed of 28 members from 13 departments or sections. Program members have $3.1M in extramural funding of which 57.9% is from the NCI (excludes $.7M training). Among the 240 publications by CBB Program members, 29% were intra-programmatic, 22% were inter-programmatic, and 59% were inter- institutional. A robust translational thrust is indicated by having 6 members serve as co-investigators on 11 clinical trials and 40 patent applications filed for various therapeutic, imaging, and diagnostic methodologies.